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Structural basis for plant-specific type III polyketide synthase based on the X-ray crystal structure analysis and computational chemistry

Research Project

Project/Area Number 24710246
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Living organism molecular science
Research InstitutionUniversity of Toyama

Principal Investigator

MORITA Hiroyuki  富山大学, 和漢医薬学総合研究所, 教授 (20416663)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords生合成 / ポリケタイド合成酵素 / 酵素工学 / ポリフェノール / アルカロイド / ポリケタイド / 閉環酵素 / X線結晶構造解析 / 結晶構造解析
Research Abstract

We solved crystal structure of an octaketide synthase (OKS) F66L/N222G mutant enzyme that catalyzes the longest number of malonyl-CoA condensations to produce TW95a. Furthermore, we succeeded in producing an OKS mutant enzyme that increased enzyme activity for the formation of TW95a to approximately 1.5 times on the basis of the crystal structure. In addition, we succeeded in cloning a novel type III PKS that specifically catalyzes the formation of quinolinone.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (50 results)

All 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (38 results) (of which Invited: 8 results)

  • [Journal Article] Two New Diphenylmethyl-Substituted Xanthones from Securidaca longepedunculata2014

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Nat. Prod. Comm.

      Volume: (In press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Muchimangins E and F : Novel Diphenylmethyl-Substituted Xanthones from Securidaca longepedunculata2014

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Tetrahedron Lett.

      Volume: 55 Pages: 1916-1919

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Muchimangins E and F: novel diphenylmethyl-substituted xanthones from Securidaca longepedunculata2014

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Tetrahedron Lett.

      Volume: 55 Issue: 11 Pages: 1916-1919

    • DOI

      10.1016/j.tetlet.2014.01.149

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two new diphenylmethyl-substituted xanthones from Securidaca longepedunculata2014

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Nat. Prod. Comm.

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heptaoxygeneted Xanthones as Anti-austerity Agents from Securidaca longepedunculata2013

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 21 Pages: 7663-7668

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cloning and Structure-Function Analyses of Quinolone- and Acridone-Producing Novel Type III Polyketide Synthases from Citrus microcarpa2013

    • Author(s)
      Takahiro Mori, Yoshihiko Shimokawa, Takashi Matsui, Keishi Kinjo, Ryohei Kato, Hiroshi Noguchi, Shigetoshi Sugio, Hiroyuki Morita, Ikuro Abe
    • Journal Title

      J . Biol. Chem.

      Volume: 288 Pages: 28845-28858

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cloning and structure-function analyses of quinolone- and acridone-producing novel type III polyketide synthases from Citrus microcarpa2013

    • Author(s)
      Mori, T., Shimokawa, Y., Matsui, T., Kinjo, K., Kato, R., Noguchi, H., Sugio, S., Morita, H., Abe, I.
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 40 Pages: 28845-28858

    • DOI

      10.1074/jbc.m113.493155

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heptaoxygeneted xanthones as anti-austerity agents from Securidaca longepedunculata2013

    • Author(s)
      Dya Fita Dibwe, Suresh Awale, Shigetoshi Kadota, Hiroyuki Morita, Yasuhiro Tezuka
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 21 Issue: 24 Pages: 7663-7668

    • DOI

      10.1016/j.bmc.2013.10.027

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Cloning and Characterization of Copper Amine Oxidase from Huperzia serrata2012

    • Author(s)
      Jieyin Sun, Hiroyuki Morita, Guoshen Chen, Hiroshi Noguchi, Ikuro Abe
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 22 Pages: 5784-5790

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prenylation of A Nonaromatic Carbon of Indolylbutenone by A Fungal Indole Prenyltransferase2012

    • Author(s)
      Jing Chen, Hiroyuki Morita, Toshiyuki Wakimoto, Takahiro Mori, Hiroshi Noguchi, Ikuro Abe
    • Journal Title

      Org. Lett.

      Volume: 14 Pages: 3080-3083

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induced production of mycotoxins in an endophytic fungus from the medicinal plant Datura stramonium L.2012

    • Author(s)
      J. Sun, T. Awakawa, H. Noguchi, I. Abe
    • Journal Title

      Bioorg. & Med. Chem. Lettr.

      Volume: 22(20) Issue: 18 Pages: 6397-6400

    • DOI

      10.1016/j.bmcl.2012.07.102

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prenylation of a nonaromatic carbon of indolylbutenone by a fungal indole prenyltransferase2012

    • Author(s)
      Chen, J.
    • Journal Title

      Organic Letters

      Volume: 14 Issue: 12 Pages: 3080-3083

    • DOI

      10.1021/ol301129x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] アサ由来オリベトール酸閉環酵素のあらたな酵素触媒機能の開拓2014

    • Author(s)
      森田洋行, 楊新美, 松井崇, 阿部郁朗
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県)
    • Year and Date
      2014-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 芳香族ドデカケタイドを生産する機能改変型アロエ由来III型ポリケタイド合成酵素のX 線結晶構造解析2014

    • Author(s)
      松井崇, 大瀧翔太, 孫昊, 阿部郁朗, 森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県)
    • Year and Date
      2014-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒメハギ科植物Securidaca longepedunculata より単離されたMuchimangin 類の合成研究2014

    • Author(s)
      児玉猛, Dya Fita Dibwe, 松井崇, 森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県)
    • Year and Date
      2014-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Polyoxygenated cyclohexane from aempferia rotunda and their cytotoxic activity2014

    • Author(s)
      Subehan , 森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県)
    • Year and Date
      2014-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Preferential Cytotoxicityof Citrus microcarpa peel against Pancreatic Cancer Cell Lines in Nutrient Deprived Conditions2014

    • Author(s)
      Dya Fita Dibwe, 李雪林, 松井崇, 手塚康弘, 森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県)
    • Year and Date
      2014-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Structural diversity of plant polyketide scaffolds2014

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Scientific Workshop For Natural Products Chemistry Program
    • Place of Presentation
      フエ大学(ベトナム)
    • Year and Date
      2014-03-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Prenylation of polyketides and alkaloids by exploring indole prenyltransferase for drug discovery2013

    • Author(s)
      Hiroyuki Morita
    • Organizer
      International Conference on Medicinal Chemistry and Timmerman Award 2013 (ICMCTA2013)
    • Place of Presentation
      インドネシア大学(インドネシア)
    • Year and Date
      2013-11-30
    • Related Report
      2013 Final Research Report
  • [Presentation] 植物ポリフェノールの骨格生合成酵素群に学ぶ化合物の多様性2013

    • Author(s)
      森田洋行
    • Organizer
      和漢医薬学総合研究所第34回特別セミナー
    • Place of Presentation
      富山国際会議場(富山県)
    • Year and Date
      2013-10-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Engineering of plant type III polyketides synthase2013

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Seminar on Campus Asia Program University of Toyama 2013
    • Place of Presentation
      慶熙大学校(韓国)
    • Year and Date
      2013-07-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Structural diversity of plant polyphenol scaffolds2013

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Seminar between International Cooperative Center for Researches of Medicinal Resources at Pekin University & Institute of Natural Medicine, University of Toyama
    • Place of Presentation
      北京大学(中国)
    • Year and Date
      2013-03-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Studies on biosynthesis of plant polyphenol scaffolds2013

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Seminar on Campus Asia Program niversity of Toyama 2013
    • Place of Presentation
      ハサヌディン大学(インドネシア)
    • Year and Date
      2013-02-06
    • Related Report
      2013 Final Research Report
  • [Presentation] New insight into substrate promiscuity and catalytic versatility of a fungal indole prenyltransferase2013

    • Author(s)
      Hiroyuki Morita, Ikuro Abe
    • Organizer
      Enzyme Engineering XXII : Emerging Topics in Enzyme Engineering
    • Place of Presentation
      富山国際会議場(富山県)
    • Related Report
      2013 Final Research Report
  • [Presentation] 芳香族ドデカケタイドを生産する機能改変型アロエ由来ポリケタイド合成酵素の結晶構造解析2013

    • Author(s)
      森田洋行, 大瀧翔太, 松井崇, 阿部郁朗
    • Organizer
      日本生薬学会第60回年会
    • Place of Presentation
      北海道医療大学(北海道)
    • Related Report
      2013 Final Research Report
  • [Presentation] コンゴ産Securidaca longepedunculataから単離したMuchimanginsの構造決定及び合成研究2013

    • Author(s)
      児玉猛,Dya Fita Dibwe,森田洋行
    • Organizer
      第48回天然物化学談話会
    • Place of Presentation
      アヤハレークサイドホテル(滋賀県大津市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 芳香族ドデカケタイドを生産する機能改変型アロエ由来ポリケタイド合成酵素の結晶構造解析2013

    • Author(s)
      森田洋行,大瀧翔太,松井崇,阿部郁朗
    • Organizer
      日本生薬学会第60回年会
    • Place of Presentation
      北海道医療大学(北海道石狩郡)
    • Related Report
      2013 Annual Research Report
  • [Presentation] New insight into substrate promiscuity and catalytic versatility of a fungal indole prenyltransferase2013

    • Author(s)
      Hiroyuki Morita, Ikuro Abe
    • Organizer
      Enzyme Engineering XXII: Emerging Topics in Enzyme Engineering
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] インドールプレニル基転移酵素の動的立体構造基盤の確立と酵素触媒機能の拡張2013

    • Author(s)
      森田洋行
    • Organizer
      新学術領域研究生合成マシナリー 第6回公開シンポジウム
    • Place of Presentation
      千葉大学(千葉県千葉市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Structural diversity of plant polyphenol scaffolds2013

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Seminner between International Cooperative Center for researches of Medicinal Resources at Pekin Univeristy & Institute of Natural Medicine, Univeristy of Toyama
    • Place of Presentation
      Peking University, China
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Studies on biosynthesis of plant polyphenol scaffolds2013

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Sminar on Campus Asia Program University of Toyama 2013
    • Place of Presentation
      Hasanuddin University, Indonesia
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 植物ポリケタイド合成酵素を利用した分子多様性の創出2012

    • Author(s)
      森田洋行
    • Organizer
      文部科学省戦略的研究基盤形成支援事業「疾患関連遺伝子及び疾患治療に用いる天然有機化合物の生合成遺伝子の包括的解析」
    • Place of Presentation
      徳島文理大学(徳島県)
    • Year and Date
      2012-12-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 二次代謝酵素のX線結晶構造解析と非天然型化合物群の創出2012

    • Author(s)
      森田洋行
    • Organizer
      第4回生合成マシナリー札幌セミナー
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2012-11-27
    • Related Report
      2013 Final Research Report
  • [Presentation] 植物ポリケタイド合成酵素の結晶構造解析と酵素工学に関する研究2012

    • Author(s)
      森田洋行
    • Organizer
      第68回酵素工学研究会講演会
    • Place of Presentation
      東京大学(東京都)
    • Year and Date
      2012-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 植物ポリケタイド合成酵素を利用した分子多様性の創出2012

    • Author(s)
      森田洋行
    • Organizer
      文部科学省戦略的研究基盤形成支援事業「疾患関連遺伝子及び疾患治療に用いる天然有機化合物の生合成遺伝子の包括的解析」第5回研究報告会
    • Place of Presentation
      徳島文理大学、徳島県
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 二次代謝酵素のX線結晶構造解析と非天然型化合物群の創出2012

    • Author(s)
      森田洋行
    • Organizer
      第4回生合成マシナリー札幌セミナー
    • Place of Presentation
      北海道大学、北海道
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 植物ポリケタイド合成酵素の結晶構造解析と酵素工学に関する研究2012

    • Author(s)
      森田洋行
    • Organizer
      第68回酵素工学研究会講演会
    • Place of Presentation
      東京大学、東京都
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] インドールプレニル基転移酵素の動的立体構造基盤の確立と酵素触媒機能の拡張

    • Author(s)
      森田洋行
    • Organizer
      新学術領域研究生合成マシナリー 第5回公開シンポジウム
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Engineering of plant type III polyketides synthase

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Seminar on Campus Asia Program University of Toyama 2013
    • Place of Presentation
      慶熙大学校(韓国ソウル)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 植物ポリフェノールの骨格生合成酵素群に学ぶ化合物の多様性

    • Author(s)
      森田洋行
    • Organizer
      和漢医薬学総合研究所第34回特別セミナー
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Prenylation of polyketides and alkaloids by exploring indole prenyltransferase for drug discovery

    • Author(s)
      Hiroyuki Morita
    • Organizer
      International Conference on Medicinal Chemistry and Timmerman Award 2013 (ICMCTA2013)
    • Place of Presentation
      インドネシア大学(インドネシア・ジャカルタ)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Directed evolution of botryococcene synthetic enzymes using random mutation

    • Author(s)
      Shusaku Sahashi, Atsuto Kimura, Takayoshi Awakawa, Hiroyuki Morita, Akinori Katabami, Daisuke Umeno, Shigeru Okada, Ikuro Abe
    • Organizer
      International Conference on Medicinal Chemistry and Timmerman Award 2013 (ICMCTA2013)
    • Place of Presentation
      インドネシア大学(インドネシア・ジャカルタ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Structural diversity of plant polyketide scaffolds

    • Author(s)
      Hiroyuki Morita
    • Organizer
      Scientific Workshop For Natural Products Chemistry Program
    • Place of Presentation
      フエ大学(ベトナム・フエ)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 放線菌由来新規インドールプレニルトランスフェラーゼTldCとMpnDの機能解析

    • Author(s)
      森貴裕,張驪駻,淡川孝義,脇本敏幸,森田洋行,阿部郁朗
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アサ由来オリベトール酸閉環酵素のあらたな酵素触媒機能の開拓

    • Author(s)
      森田洋行,楊新美,松井崇,阿部郁朗
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 芳香族ドデカケタイドを生産する機能改変型アロエ由来III型ポリケタイド合成酵素のX線結晶構造解析

    • Author(s)
      松井崇,大瀧翔太,孫昊,阿部郁朗,森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒメハギ科植物Securidaca longepedunculataより単離されたMuchimangin類の合成研究

    • Author(s)
      児玉猛,Dya Fita Dibwe, 松井崇,森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Polyoxygenated cyclohexane from Kaempferia rotunda and their cytotoxic activity

    • Author(s)
      Subehan,森田洋行
    • Organizer
      日本薬学会第134年
    • Place of Presentation
      熊本市総合体育館(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Preferential Cytotoxicity of Citrus microcarpa peel against Pancreatic Cancer Cell Lines in Nutrient Deprived Conditions

    • Author(s)
      Dya Fita Dibwe,李雪林, 松井崇, 手塚康弘, 森田洋行
    • Organizer
      日本薬学会第134年
    • Place of Presentation
      熊本市総合体育館(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Preferential cytotoxic constituents from Aframomum melegueta against human pancreatic cancer cell line

    • Author(s)
      手塚康弘,Dya Fita Dibwe,Suresh Awale,森田洋行
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本市総合体育館(熊本県熊本市)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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